Ethanol Oxidation by Hydroxyl Radicals: Role of Iron Chelates, Superoxide, and Hydrogen Peroxide

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Abstract
Oxygen‐derived free radicals such as the hydroxyl radical (OH) have been shown to mediate the oxidation of ethanol by a variety of oxy radical‐generating systems. Among these are microsomal electron transport systems (both intact and purified, reconstituted systems), the coupled oxidation of hypoxanthine or xanthine by xanthine oxidase, and the model ironascorbate system. The sequence of reactions leading to the oxy radical‐dependent oxidation of ethanol as was as other hydroxyl radical‐scavenging agents by these various systems is believed to proceed through the formation of a common intermediate, namely, hydrogen peroxide (H2O2), after disrmitation of the superoxide anion radical (O2−). The presence of iron, especially chelated iron, greatly enhances the production of OH by serving as an oxidant for O2− or a reductant for H2O2 Experiments were carried out to evaluate the role of iron, the chelating agent, 02−, and H2O2 in the oxidation of ethanol by a variety of in vitro systems (chemical, enzymatic, and intact membrane bound) that can produce oxy radicals via different mechanisms. The generation of OH by aN the systems studied was sensitive to catalase, which indicates that H1O2 is the precursor of OH. Superoxide radical appears to be the reducing agent in the hypoxanthine‐xanthine oxidase system, indicating an iron‐catalyzed Haber‐Weiss reaction. In the ascorbate, reductase, and microsomal systems, superoxide radical does not appear to be the reducing agent However, superoxide radical probably is the precursor of H*0. While iron plays an important role in the production of OH by the various systems, the effect of iron depends on the nature of the iron chelate. For example, ferric‐EDTA is always stimulatory, whereas desferoxamine is always inhibitory. Certain iron chelates work in one system but not in another. In the reductase‐dependent systems, only those iron chelates that stimulated NADPH oxidation stimulated OH scavenger and ethanol oxidation. These data suggest that the ability of iron to promote OH production and ethanol metabolism depends on the nature of the system which must take into account the reductant, the chelating agent, and the OH scavenger employed. Hence, the role of iron as a mediator of oxidative processes is complex, and further studies will be required in order to understand the role of iron and, in particular, physmlogicalry relevant iron chelates in promoting lipid peroxidation and the production of oxy radicals, and the interaction of ethanol with oxygen radicals derived from various systems.

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